The present invention relates to a process for preparing nucleoside acid derivatives useful as antiviral agents. In particular, the invention relates to a process for preparing nucleoside derivatives by alkylating purine bases.
It is known that 2-amino-9-[(1'S,2'R)-1',2'-bis(hydroxymethyl)cyclopropane-1'-yl]methylpuri ne represented by the following formula (1) and 9-[(1'S,2'R)-1',2'-bis(hydroxymethyl)cyclopropane-1'-yl]methylguanine represented by the following formula (2) have a strong antiviral activity [Japanese Patent Unexamined Published Application (hereinafter referred to as "J. P. KOKAI") Nos. Hei 5-78357 and Hei 6-227982]. ##STR1##
It is also known that the compounds of the above formulae (1) and (2) are produced by alkylating protected purine bases to obtain corresponding purine bases alkylated at the N-7 position and N-9 position and purifying them by silica gel column chromatography and removing the protecting group (J. P. KOKAI Nos. Hei 6-80670 and Hei 7-316155.
It is generally known that in the preparation of the antiviral agents by the condensation reaction of a purine base and an alkylating agent, the alkylation reaction occurs at both N-7 position and N-9 position of the purine base as described above. Since the intended compound is usually the purine base substituted at the N-9 position, conventionally it was inevitable to isolate it by the column chromatography.